p27(Kip1)-stathmin interaction influences sarcoma cell migration and invasion

Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate cellular functions other than cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27(kip1) affects microtubule (MT) stability following cell adhesion on e...

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Bibliographic Details
Published in:Cancer cell 2005-01, Vol.7 (1), p.51-63
Main Authors: Baldassarre, Gustavo, Belletti, Barbara, Nicoloso, Milena S, Schiappacassi, Monica, Vecchione, Andrea, Spessotto, Paola, Morrione, Andrea, Canzonieri, Vincenzo, Colombatti, Alfonso
Format: Article
Language:English
Subjects:
Animals
Cell Adhesion
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cell Line, Tumor
Cell Movement
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p27
Enzyme Inhibitors - metabolism
Extracellular Matrix - metabolism
Fibroblasts - cytology
Fibroblasts - physiology
Fibronectins - metabolism
Genes, Tumor Suppressor
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Microtubule Proteins - genetics
Microtubule Proteins - metabolism
Microtubules - metabolism
Neoplasm Metastasis
Phenotype
Phosphoproteins - genetics
Phosphoproteins - metabolism
Sarcoma - metabolism
Sarcoma - pathology
Stathmin
Tubulin - genetics
Tubulin - metabolism
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
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Summary:Emerging evidences suggest that cyclin-dependent kinase inhibitors (CKIs) can regulate cellular functions other than cell cycle progression, such as differentiation and migration. Here, we report that cytoplasmic expression of p27(kip1) affects microtubule (MT) stability following cell adhesion on extracellular matrix (ECM) constituents. This p27(kip1) activity is due to its ability to bind and impair the function of the MT-destabilizing protein stathmin. Accordingly, upregulation of p27(kip1) or downregulation of stathmin expression results in the inhibition of mesenchymal cell motility. Moreover, high stathmin and low cytoplasmic p27(kip1) expression correlate with the metastatic phenotype of human sarcomas in vivo. This study provides a functional link between proliferation and invasion of tumor cells based on diverse activities of p27(kip1) in different subcellular compartments.
ISSN:1535-6108
DOI:10.1016/j.ccr.2004.11.025